Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a contiguous gene syndrome resulting from abnormal DNA methylation within the Prader-Willi critical region (PWCR) on chromosome 15q11.2–q13.   Diagnosis and identification of the underlying molecular mechanism in an affected individual (proband) can be effectively achieved through simultaneous DNA methylation analysis and oligo-SNP array (OSA).

DNA methylation analysis detects the presence of maternal-only imprinting at the PWCR, which is a hallmark of PWS.

The OSA provides additional insight by identifying the specific genetic subtype—such as a 15q11.2–q13 deletion, an imprinting center deletion, or cases of uniparental isodisomy and segmental isodisomy.

In individuals who show maternal-only imprinting on DNA methylation analysis but have a normal OSA result, further investigation with DNA polymorphism analysis can help distinguish between uniparental heterodisomy and an epimutation-driven imprinting defect.

Infantile period

Nutritional Support : Use of special nipples or nasogastric tube feeding to ensure adequate nutrition.

Childhood

1. Nutritional Management

• Strict supervision of food intake based on height, weight, and BMI.
• Encourage regular physical activity.

2. Growth and Hormonal Therapy

• Growth hormone (GH) to normalize height, increase lean body mass and mobility, and reduce fat mass.
• Sex hormone replacement at puberty as needed.
• Treatment for cryptorchidism (hormonal or surgical).
• Management of precocious puberty, type 2 diabetes, and hypothyroidism.

3. Medical Management

• Urgent evaluation for acute gastrointestinal symptoms.
• Topiramate or N-acetylcysteine for skin picking.
• Standard treatments for : neurobehavioral and psychiatric symptoms, ophthalmologic issues, sleep disturbances, scoliosis, hip dysplasia, and seizures

4. Bone Health

• Calcium and vitamin D supplementation to prevent osteoporosis.
• Consider sex steroids, GH, or bisphosphonates for low bone density.

Adulthood

• Residential Support: Structured residential facilities for behavior and weight management to prevent morbid obesity.
• Hormonal Therapy: Continued GH therapy to help maintain muscle mass.